The subject matter herein relates generally to systems and methods of loading or removing liquids and, more specifically, to systems and methods of loading reagents or removing waste from assay systems that use the liquids for biochemical analysis.
Various protocols in biological or chemical analysis involve performing a large number of controlled reactions at designated support surfaces or within designated reaction chambers. The reactions may then be observed, detected, or otherwise analyzed to identify or reveal properties of chemicals involved in the reactions. One technology used to conduct such reactions is digital fluidics (DF). DF uses electrowetting-mediated operations to move and manipulate droplets of liquid. The droplets may be located within a DF device, such as an enclosed cartridge, that includes one or more substrates configured to form a surface or gap for conducting droplet operations. The substrate(s) or the gap may be coated or filled with a filler liquid that is immiscible with respect to the liquid that forms the droplets. Electrodes are arranged within or along the substrate(s) and are configured to provide different electric fields in accordance with a predetermined sequence to transport, mix, filter, monitor, and/or analyze liquid within the DF device. Various assay protocols may be performed by manipulating the droplets. By way of example only, DF technology may be used in quantitative analysis of DNA (qPCR) and RNA (RT-qPCR), protein analysis using both enzymatic and immunoassay techniques, DNA sequencing (e.g., sequencing-by-synthesis), sample preparation, and preparation of fragment libraries for next generation sequencing. DF technology has also been proposed for manufacturing lab-on-chip (LOC) devices, such as disposable single-use devices, that are capable of performing a particular assay protocol.
At least some DF devices are configured to perform a particular assay protocol that includes a relatively limited number of reactions. Upon completion of the assay, the DF device may be discarded. It may be desirable to have DF devices that are capable of performing more reactions than the known DF devices and/or that are capable of being re-used for different assays. Increasing the number of reactions, however, requires a larger amount of reagents. It can be difficult to load liquids into the DF devices because of the small size of the DF devices and the small volumes of reagents that are used when performing the assays. Moreover, a large number of different reagents may be used. For example, in some applications, thirty-two different reagents must be loaded into the DF device.
DF devices are often manually loaded using pipettes or syringes. Manual loading carries a risk of user error and/or contamination and can be costly. For instance, if a single reagent is loaded into an incorrect port of the DF device, it may be necessary to discard the entire DF device. Although loading methods have been proposed, such methods may not be commercially reasonable and/or may not fully address the loading challenges discussed above.
One potential consequence in increasing the number of reactions is that a larger amount of liquid waste may accumulate within the system. In at least some known devices, the liquid waste is never removed from the system. For example, the liquid waste is permitted to accumulate within the DF device and is discarded with the DF device after the assay protocol has been completed. If systems are configured to conduct a greater number of reactions and/or be re-used, it may be necessary to remove the waste during operation of the DF device or without disposing of the entire DF device.
Other than DF devices, various types of assay systems may benefit from improved liquid loading and/or removal. For example, continuous-flow assay systems often mix a number of reagents into a common flow channel using a multi-purpose valve. The mixture may then be directed through a fluidic device, such as a flow cell, where designated reactions occur and are detected.
Accordingly, there is a need for methods and systems that are capable of loading and/or removing one or more liquids used by fluidic systems.